ABSTRACT: Dissemination of High-Risk and Novel ESBL-Producing E. coli Clones Across One Health Interfaces in Nine African Countries: A Whole-Genome Perspective from the SeqAfrica-FAO Network
Project description:Background: It remains unclear how high-risk Escherichia coli lineages, like sequence type (ST) 131, initially adapt to carbapenem exposure in its progression to becoming carbapenem resistant. Methods: Carbapenem mutation frequency was measured in multiple subclades of extended-spectrum β-lactamase (ESBL) positive ST131 clinical isolates using a fluctuation assay followed by whole genome sequencing (WGS) characterization. Genomic, transcriptomic, and porin analyses of ST131 C2/H30Rx isolate, MB1860, under prolonged, increasing carbapenem exposure was performed using two distinct experimental evolutionary platforms to measure fast vs. slow adaptation. Results: All thirteen ESBL positive ST131 strains selected from a diverse (n=184) ST131 bacteremia cohort had detectable ertapenem (ETP) mutational frequencies with a statistically positive correlation between initial ESBL gene copy number and mutation frequency (r = 0.87, P<1e-5). WGS analysis of mutants showed initial response to ETP exposure resulted in significant increases in ESBL gene copy numbers or mutations in outer membrane porin (Omp) encoding genes in the absence of ESBL gene amplification with subclade specific adaptations. In both experimental evolutionary platforms, MB1860 responded to initial ETP exposure by increasing blaCTX-M-15 copy numbers via modular, insertion sequence 26 (IS26) mediated pseudocompound transposons (PCTns). Transposase activity driven by PCTn upregulation was a conserved expression signal in both experimental evolutionary platforms. Stable mutations in Omp encoding genes were detected only after prolonged increasing carbapenem exposure consistent with clinical observations. Conclusions: ESBL gene amplification is a conserved response to initial carbapenem exposure, especially within the high-risk ST131 C2 subclade. Targeting such amplification could assist with mitigating carbapenem resistance development.
2024-08-04 | GSE273456 | GEO
Project description:Metagenome-Assembled Genomes of Pig Fecal Samples in Nine European Countries
Project description:The present study examines changes in global gene expression patterns and in virulence factor-associated genes in an extended spectrum beta-lactamase (ESBL)-producing UPEC (ESBL019) during the morphologic transitions induced by an ineffective antibiotic and in the presence of human primary bladder epithelial cells. The morphological shifts induced by ineffective antibiotics are associated with significant transcriptional virulence alterations in ESBL-producing UPEC, which may affect survival and persistence in the urinary tract.
Project description:Colectomy is the most commonly used therapeutic approach for the treatment of non-metastatic colorectal cancer. This approach is generally very effective however the rate of recurrence and the appearance of metachronous metastasis remains a major problem in the postoperative period. One of the hypothesis that can explain this tumor progression is the dissemination of tumor cells at the time of tumor mobilization. In this work, we wish to verify this hypothesis by comparing two surgical technics used in our department for left or right colectomies: respectively either first section of the mesenteric vessels followed by the mobilization of the tumor or first mobilization of the tumor followed by the section of the mesenteric vessels. To evaluate the dissemination, we will study two disseminations markers that have shown their prognostic value: i) circulating tumor cells (which represent a direct marker of dissemination) and ii) tumor circulating DNA (which is an indirect marker) but has the advantage of being more representative of all tumor clones and therefore the tumor burden released into the blood at the time of surgery).
| 2294763 | ecrin-mdr-crc
Project description:Metagenome-Assembled Genomes of Pig Fecal Samples in Nine European Countries part 11
| PRJNA1186149 | ENA
Project description:Metagenome-Assembled Genomes of Pig Fecal Samples in Nine European Countries part 3
| PRJNA1186113 | ENA
Project description:Metagenome-Assembled Genomes of Pig Fecal Samples in Nine European Countries part 10
| PRJNA1186148 | ENA
Project description:Metagenome-Assembled Genomes of Pig Fecal Samples in Nine European Countries part 4
